Dapagliflozin in Non Alcoholic Fatty Liver Disease Associated Cirrhosis and Its Role in Preventing Development of Chronic Kidney Disease.

Sponsor

Institute of Liver and Biliary Sciences, India (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05849220

Collaborator

(none)

144

Enrollment

Location

Arms

10.5

Anticipated Duration (Months)

13.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The role of Dapagliflozin in the improvement in CKD in both diabetic and non-diabetic patients has been evaluated in the past. SGLT2i have also been found to be beneficial in NAFLD patients in improving the liver function parameters. It is also known that cirrhotic patients are at a higher risk of developing CKD at 1 year when compared to non cirrhotics. With this study we aim to study the role Dapagliflozin in cirrhotic patients in reducing the development of CKD, its impact on cirrhotic cardiomyopathy and its role in improvement of metabolic profile and liver related outcomes.

Condition or Disease	Intervention/Treatment	Phase
NAFLD Cirrhosis	Drug: Dapagliflozin Other: Standard of Care	N/A

Detailed Description

Hypothesis: Investigator hypothesise that Use of Dapagliflozin in NAFLD-Cirrhotic patients with moderate ascites will prevent progression and development of chronic kidney disease, ameliorate metabolic dysfunction and facilitate resolution of ascites by its renoprotective, cardioprotective and metabolic effects

Aim: To evaluate the efficacy of Dapagliflozin in NAFLD-cirrhotic patients with moderate ascites in preventing progression and development of CKD

Methodology:

Study population:

Age > 18 years <70 years
Patient with NAFLD associated cirrhosis and moderate ascites
Stable eGFR-(>60 ml/min/1.73m2) calculated using MDRD-6 equation: eGFR (ml/min/1.73 m2) = 198 × [serum creatinine (mg/dL)]-0. 858 × [age]-0. 167 × [0.822 if patient is female] × [serum urea nitrogen concentration (mg/dL)]-0.

Study design: Monocentric open label randomised controlled study. The study will be conducted in Department of Hepatology, ILBS.

Study period: 1 year

Sample size: Based on the previous study, assuming that progression rate in standard arm for chronic kidney disease is 30% and with addition of Dapagliflozin Investigator expect that there will be an absolute reduction of 20% in progression, i.e. 10 % progression rate

Alpha - 5%
Power - 80
10 % dropout rate
Investigator need to enrol approximately 144 patients with 72 patients in each arm allocated into two groups by block randomization method taking block size of 10.

Patients will be evaluated in OPD for stable eGFR (based on the creatinine value in the last 3 months)

Intervention Patients after screening for all exclusion criteria will be randomised into 2 arms (group-1, receiving Dapagliflozin) and (group-2, standard of care) in a ratio 1:1

Monitoring and assessment Both the groups will undergo baseline investigations including KFT, Urine routine and microscopy, LFT, Fibroscan liver and spleen, baseline 2decho, ECG, NTproBNP, biomarkers of inflammation, renal reserve and metabolic profile incuding Hba1c, FBS, S.lipid profile, waist circumference, HOMA-IR, BMI, Bone mineral density(DEXA), liver frailty index, 6 min walk test and hand grip analysis.

All the patients will be followed in OPD at 3 monthly intervals and biomarkers of renal reserve and inflammation will be repeated at 6 monthly interval.

STATISTICAL ANALYSIS: Continuous data- Student's t test

Nonparametric analysis- Mann Whitney test
Survival outcome By Kaplan-Meier method curve.
For all tests, p≤ 0.05 will be considered statistically significant.
Analysis will be performed using SPSS.
The analysis will be done with intention to treat and per protocol analysis if applicable.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dapagliflozin in Non Alcoholic Fatty Liver Disease Associated Cirrhosis and Its Role in Preventing Development of Chronic Kidney Disease. A Randomized Controlled Trial.

Anticipated Study Start Date :

May 15, 2023

Anticipated Primary Completion Date :

Mar 30, 2024

Anticipated Study Completion Date :

Mar 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dapagliflozin+Standard of Care Dapagliflozin	Drug: Dapagliflozin Dapagliflozin Other: Standard of Care Standard of Care
Active Comparator: Standard of Care Standard of Care	Other: Standard of Care Standard of Care

Arm

Intervention/Treatment

Experimental: Dapagliflozin+Standard of Care

Dapagliflozin

Drug: Dapagliflozin

Dapagliflozin

Other: Standard of Care

Standard of Care

Active Comparator: Standard of Care

Standard of Care

Other: Standard of Care

Standard of Care

Outcome Measures

Primary Outcome Measures

Number of participants developing Chronic Kidney Disease at 1 yr defined as per KDIGO guidelines. [1 year]

Secondary Outcome Measures

Number of participants developing Chronic Kidney Disease. [3 months]
Number of participants developing Chronic Kidney Disease. [6 months]
Improvement in eGlomerular filtration rate (eGFR) at 3 months. [3 months]
Change in eGlomerular filtration rate (eGFR) at 6 months. [6 months]
Change in eGlomerular filtration rate (eGFR) at 12 months. [12 months]
Number of participants developing acute kidney disease at 3 months. [3 months]
Number of participants developing acute kidney disease at 6 months. [6 months]
Number of participants developing acute kidney disease at 12 months. [12 months]
Number of participants Discontinuing drug due to adverse effects. [1 year]
Number of participants with resolution of ascites - partial or complete at 3 months. [3 months]
Number of participants with resolution of ascites - partial or complete at 6 months. [6 months]
Number of participants with resolution of ascites - partial or complete at 12 months. [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years <70years
Patient with NAFLD associated cirrhosis and moderate ascites
Stable eGFR-(>60 ml/min/1.73m2) calculated using MDRD-6 equation: eGFR (ml/min/1.73 m2) = 198 × [serum creatinine (mg/dL)]-0. 858 × [age]-0. 167 × [0.822 if patient is female] × [serum urea nitrogen concentration (mg/dL)]-0.
Valid Informed written consent

Exclusion Criteria:

Hospitalized patients
CTP-C patients
Intrinsic/structural kidney disease, obstructive uropathy, ADPKD, Anatomic urologic defects that predispose to urinary tract infection
History of organ transplantation
Refractory Ascites
Type 1 DM
History of hypoglycemic symptoms in the last 2 months
Recurrent UTI
Patient with HCC or portal vein thrombosis
Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
History of fracture in the preceding year
Severe Hyponatremia (Na <125 MEq/L)
Pregnancy or Lactating mother
Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
MI, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment
Coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement within 12 weeks prior to enrolment or is planned to undergo any of these procedures after randomization
Mixed ascites (additional etiology of ascites apart from portal hypertension)
Any severe extra hepatic condition including respiratory and cardiac failure
Acute-on-chronic liver failure as per the APASL criteria
Refusal to give consent